The importance of timing differentiation during limb muscle development
The importance of timing differentiation during limb muscle development
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DOI：
10.1016/s0960-9822(98)70251-9
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发表时间：
1998-05-21
期刊：
影响因子：
9.2
通讯作者：
Patel, K
中科院分区：
文献类型：
--
作者：
Amthor, H;Christ, B;Patel, K
背景：躯干、四肢和舌头的骨骼肌由源自体节的一小群细胞发育而来。尽管肌肉分化的促进剂和抑制剂已被分离出来，但对于如何调节肌肉前体库的扩增却一无所知。这种放大在发育过程中提供了肌肉质量。此外，人们对细胞如何在四肢前肌团中积累知之甚少。我们研究了骨形态发生蛋白 (BMP) 和音刺猬 (Shh) 在肌肉增殖、分化和定位过程中的作用。结果：四肢肌肉前体细胞的增殖与 Pax-3 表达相关。外胚层去除会下调 Pax-3 表达、抑制增殖并过早启动肌肉分化，从而耗尽肌肉前体池并阻止进一步的肌肉生长。 BMP-2、BMP-4和BMP-7对肌原细胞具有剂量依赖性作用：低浓度维持表达Pax-3的增殖群体，取代外胚层衍生的增殖信号并延迟分化，而高浓度可能通过诱导细胞凋亡来阻止肌肉发育。在肢体中，Shh 上调 Bmp-2 和 Bmp-7 表达，从而延迟肌肉分化，上调 Pax-3，扩增肌肉前体群体并刺激过度肌肉生长。结论：这些数据表明胚胎肌肉生长需要延迟肌肉分化。细胞逃避增殖信号后，肌肉分化可能会通过默认途径发生。肌肉的定位受到高浓度 BMP 的调节，因此单一类型的信号分子可以决定肌肉发育的关键步骤：何时何地增殖，何时何地分化。 (C) Current Biology Ltd ISSN 0960-9822。
Background: Skeletal muscle of trunk, limbs and tongue develops from a small population of cells that originates from somites. Although promoters and inhibitors of muscle differentiation have been isolated, nothing is known about how the amplification of the muscle precursor pool is regulated; this amplification provides muscle mass during development. Furthermore, little is known about how cells accumulate in the pre-muscle masses in the limbs. We investigated the role of bone morphogenetic proteins (BMPs) and Sonic hedgehog (Shh) during proliferation, differentiation and positioning of muscle.Results: The proliferation of muscle precursors in limbs was linked to Pax-3 expression. Ectoderm removal downregulated Pax-3 expression, arrested proliferation and prematurely initiated muscle differentiation which exhausted the muscle precursor pool and prevented further muscle growth. BMP-2, BMP-4 and BMP-7 had a dose-dependent effect on pre-myogenic cells: low concentrations maintained a Pax-3-expressing proliferative population, substituting for ectoderm-derived proliferative signals and delaying differentiation, whereas high concentrations prevented muscle development, probably by inducing apoptosis. In the limb, Shh upregulated Bmp-2 and Bmp-7 expression which delayed muscle differentiation, upregulated Pax-3, amplified the muscle precursor population and stimulated excessive muscle growth.Conclusions: These data indicate that embryonic muscle growth requires muscle differentiation to be delayed. Muscle differentiation may occur through a default pathway after cells escape proliferative signals. Positioning of muscle is regulated by high concentrations of BMPs, thus a single type of signalling molecule can determine crucial steps in muscle development: when and where to proliferate, and when and where to differentiate. (C) Current Biology Ltd ISSN 0960-9822.